Saint Louis University (SLU)
We have shown that erythrocytes released ATP in response to physiological stimuli and that this ATP regulates perfusion distribution in skeletal muscle and stimulates pulmonary vasodilation. We have characterized signaling pathways for ATP release from erythrocytes and have identified defects in these pathways in humans with type 2 diabetes (DM2) and pulmonary arterial hypertension (PAH). Our ability to link physiological stimuli to various elements of the signaling pathways required for erythrocyte ATP release is essential for developing new and innovative pharmacological approaches to augment vasodilation. These approaches, coupled with the ability to determine the contribution of erythrocytes and pharmacological agents to the responses of isolated resistance vessels, makes our laboratory ideal for determination of the role erythrocyte-released ATP in vascular control. The ability to improve ATP release from erythrocytes of humans with DM2 and PAH is a major translational outcome of the proposed studies.